Nuclear magnetic resonance studies of molecular interactions and structures

This thesis is concerned with the investigation, by nuclear magnetic resonance spectroscopy, of the molecular interactions occurring in mixtures of benzene and cyclohexane to which either chloroform or deutero-chloroform has been added. The effect of the added polar molecule on the liquid structure has been studied using spin-lattice relaxation time, 1H chemical shift, and nuclear Overhauser effect measurements. The main purpose of the work has been to validate a model for molecular interaction involving local ordering of benzene around chloroform. A chemical method for removing dissolved oxygen from samples has been developed to encompass a number of types of sample, including quantitative mixtures, and its supremacy over conventional deoxygenation technique is shown. A set of spectrometer conditions, the use of which produces the minimal variation in peak height in the steady state, is presented. To separate the general diluting effects of deutero-chloroform from its effects due to the production of local order a series of mixtures involving carbon tetrachloride, instead of deutero-chloroform, have been used as non-interacting references. The effect of molecular interaction is shown to be explainable using a solvation model, whilst an approach involving 1:1 complex formation is shown not to account for the observations. It is calculated that each solvation shell, based on deutero-chloroform, contains about twelve molecules of benzene or cyclohexane. The equations produced to account for the T1 variations have been adapted to account for the 1H chemical shift variations in the same system. The shift measurements are shown to substantiate the solvent cage model with a cage capacity of twelve molecules around each chloroform molecule. Nuclear Overhauser effect data have been analysed quantitatively in a manner consistent with the solvation model. The results show that discrete shells only exist when the mole fraction of deutero-chloroform is below about 0.08.

Elasto-plastic impact of fine particles and fragmentation of small agglomerates

Surface deposition of dense aerosol particles is of major concern in the nuclear industry for safety assessment. This study presents theoretical investigations and computer simulations of single gas-born U3O8 particles impacting with the in-reactor surface and the fragmentation of small agglomerates. A theoretical model for elasto-plastic spheres has been developed and used to analyse the force-displacement and force-time relationships. The impulse equations, based on Newton's second law, are applied to govern the tangential bouncing behaviour. The theoretical model is then incorporated into the Distinct Element Method code TRUBAL in order to perform computer simulated tests of particle collisions. A comparison of simulated results with both theoretical predictions and experimental measurements is provided. For oblique impacts, the results in terms of the force-displacement relationship, coefficients of restitution, trajectory of the impacting particle, and distribution of kinetic energy and work done during the process of impact are presented. The effects of Poisson's ratio, friction, plastic deformation and initial particle rotation on the bouncing behaviour are also discussed. In the presence of adhesion an elasto-plastic collision model, which is an extension to the JKR theory, is developed. Based on an energy balance equation the critical sticking velocity is obtained. For oblique collisions computer simulated results are used to establish a set of criteria determining whether or not the particle bounces off the target plate. For impact velocities above the critical sticking value, computer simulated results for the coefficients of restitution and rebound angles of the particle are presented. Computer simulations of fracture/fragmentation resulting from agglomerate-wall impact have also been performed, where two randomly generated agglomerates (one monodisperse, the other polydisperse), each consisting of 50 primary particles are used. The effects of impact angle, local structural arrangements close to the impact point, and plastic deformation at the contacts on agglomerate damage are examined. The simulated results show a significant difference in agglomerate strength between the two assemblies. The computer data also shows that agglomerate damage resulting from an oblique impact is determined by the normal velocity component rather than the impact speed.

Use of amino acids as counterions improves the solubility of the BCS II model drug, indomethacin

The number of new chemical entities (NCE) is increasing every day after the introduction of combinatorial chemistry and high throughput screening to the drug discovery cycle. One third of these new compounds have aqueous solubility less than 20µg/mL [1]. Therefore, a great deal of interest has been forwarded to the salt formation technique to overcome solubility limitations. This study aims to improve the drug solubility of a Biopharmaceutical Classification System class II (BCS II) model drug (Indomethacin; IND) using basic amino acids (L-arginine, L-lysine and L-histidine) as counterions. Three new salts were prepared using freeze drying method and characterised by FT-IR spectroscopy, proton nuclear magnetic resonance ((1)HNMR), Differential Scanning Calorimetry (DSC) and Thermogravimetric analysis (TGA). The effect of pH on IND solubility was also investigated using pH-solubility profile. Both arginine and lysine formed novel salts with IND, while histidine failed to dissociate the free acid and in turn no salt was formed. Arginine and lysine increased IND solubility by 10,000 and 2296 fold, respectively. An increase in dissolution rate was also observed for the novel salts. Since these new salts have improved IND solubility to that similar to BCS class I drugs, IND salts could be considered for possible waivers of bioequivalence.

A micro-compression study of shape-memory deformation in U-13 at.% Nb

Microcompression specimens, 10–15 µm in diameter by 20–30 µm in height, were produced from individual parent grains in a polycrystalline U–13 at.%Nb shape-memory alloy using the focused ion beam technique. The specimens were tested in a nanoindentation instrument with a flat diamond tip to investigate stress–strain behavior as a function of crystallographic orientation. The results are in qualitative agreement with a single-crystal accommodation strain (Bain strain) model of the shape-memory effect for this alloy.

Attenuation of muscle atrophy in a murine model of cachexia by inhibition of the dsRNA-dependent protein kinase

Atrophy of skeletal muscle is due to a depression in protein synthesis and an increase in degradation. Studies in vitro have suggested that activation of the dsRNA-dependent protein kinase (PKR) may be responsible for these changes in protein synthesis and degradation. In order to evaluate whether this is also applicable to cancer cachexia the action of a PKR inhibitor on the development of cachexia has been studied in mice bearing the MAC16 tumour. Treatment of animals with the PKR inhibitor (5 mg kg-1) significantly reduced levels of phospho-PKR in muscle down to that found in non-tumour-bearing mice, and effectively attenuated the depression of body weight, with increased muscle mass, and also inhibited tumour growth. There was an increase in protein synthesis in skeletal muscle, which paralleled a decrease in eukaryotic initiation factor 2α phosphorylation. Protein degradation rates in skeletal muscle were also significantly decreased, as was proteasome activity levels and expression. Myosin levels were increased up to values found in non-tumour-bearing animals. Proteasome expression correlated with a decreased nuclear accumulation of nuclear factor-κB (NF-κB). The PKR inhibitor also significantly inhibited tumour growth, although this appeared to be a separate event from the effect on muscle wasting. These results suggest that inhibition of the autophosphorylation of PKR may represent an appropriate target for the attenuation of muscle atrophy in cancer cachexia. © 2007 Cancer Research UK.

Characterizing permanent deformation and fracture of asphalt mixtures by using compressive dynamic modulus tests

Permanent deformation and fracture may develop simultaneously when an asphalt mixture is subjected to a compressive load. The objective of this research is to separate viscoplasticity and viscofracture from viscoelasticity so that the permanent deformation and fracture of the asphalt mixtures can be individually and accurately characterized without the influence of viscoelasticity. The undamaged properties of 16 asphalt mixtures that have two binder types, two air void contents, and two aging conditions are first obtained by conducting nondestructive creep tests and nondestructive dynamic modulus tests. Testing results are analyzed by using the linear viscoelastic theory in which the creep compliance and the relaxation modulus are modeled by the Prony model. The dynamic modulus and phase angle of the undamaged asphalt mixtures remained constant with the load cycles. The undamaged asphalt mixtures are then used to perform the destructive dynamic modulus tests in which the dynamic modulus and phase angle of the damaged asphalt mixtures vary with load cycles. This indicates plastic evolution and crack propagation. The growth of cracks is signaled principally by the increase of the phase angle, which occurs only in the tertiary stage. The measured total strain is successfully decomposed into elastic strain, viscoelastic strain, plastic strain, viscoplastic strain, and viscofracture strain by employing the pseudostrain concept and the extended elastic-viscoelastic correspondence principle. The separated viscoplastic strain uses a predictive model to characterize the permanent deformation. The separated viscofracture strain uses a fracture strain model to characterize the fracture of the asphalt mixtures in which the flow number is determined and a crack speed index is proposed. Comparisons of the 16 samples show that aged asphalt mixtures with a low air void content have a better performance, resisting permanent deformation and fracture. © 2012 American Society of Civil Engineers.

A generalized Drucker–Prager viscoplastic yield surface model for asphalt concrete

A generalized Drucker–Prager (GD–P) viscoplastic yield surface model was developed and validated for asphalt concrete. The GD–P model was formulated based on fabric tensor modified stresses to consider the material inherent anisotropy. A smooth and convex octahedral yield surface function was developed in the GD–P model to characterize the full range of the internal friction angles from 0° to 90°. In contrast, the existing Extended Drucker–Prager (ED–P) was demonstrated to be applicable only for a material that has an internal friction angle less than 22°. Laboratory tests were performed to evaluate the anisotropic effect and to validate the GD–P model. Results indicated that (1) the yield stresses of an isotropic yield surface model are greater in compression and less in extension than that of an anisotropic model, which can result in an under-prediction of the viscoplastic deformation; and (2) the yield stresses predicted by the GD–P model matched well with the experimental results of the octahedral shear strength tests at different normal and confining stresses. By contrast, the ED–P model over-predicted the octahedral yield stresses, which can lead to an under-prediction of the permanent deformation. In summary, the rutting depth of an asphalt pavement would be underestimated without considering anisotropy and convexity of the yield surface for asphalt concrete. The proposed GD–P model was demonstrated to be capable of overcoming these limitations of the existing yield surface models for the asphalt concrete.

Interpretation of the Superpave IDT strength test using a viscoelastic-damage constitutive model

This paper presents a new interpretation for the Superpave IDT strength test based on a viscoelastic-damage framework. The framework is based on continuum damage mechanics and the thermodynamics of irreversible processes with an anisotropic damage representation. The new approach introduces considerations for the viscoelastic effects and the damage accumulation that accompanies the fracture process in the interpretation of the Superpave IDT strength test for the identification of the Dissipated Creep Strain Energy (DCSE) limit from the test result. The viscoelastic model is implemented in a Finite Element Method (FEM) program for the simulation of the Superpave IDT strength test. The DCSE values obtained using the new approach is compared with the values obtained using the conventional approach to evaluate the validity of the assumptions made in the conventional interpretation of the test results. The result shows that the conventional approach over-estimates the DCSE value with increasing estimation error at higher deformation rates.

Stochastically forced dislocation density distribution in plastic deformation

The dynamical evolution of dislocations in plastically deformed metals is controlled by both deterministic factors arising out of applied loads and stochastic effects appearing due to fluctuations of internal stress. Such type of stochastic dislocation processes and the associated spatially inhomogeneous modes lead to randomness in the observed deformation structure. Previous studies have analyzed the role of randomness in such textural evolution but none of these models have considered the impact of a finite decay time (all previous models assumed instantaneous relaxation which is "unphysical") of the stochastic perturbations in the overall dynamics of the system. The present article bridges this knowledge gap by introducing a colored noise in the form of an Ornstein-Uhlenbeck noise in the analysis of a class of linear and nonlinear Wiener and Ornstein-Uhlenbeck processes that these structural dislocation dynamics could be mapped on to. Based on an analysis of the relevant Fokker-Planck model, our results show that linear Wiener processes remain unaffected by the second time scale in the problem but all nonlinear processes, both Wiener type and Ornstein-Uhlenbeck type, scale as a function of the noise decay time τ. The results are expected to ramify existing experimental observations and inspire new numerical and laboratory tests to gain further insight into the competition between deterministic and random effects in modeling plastically deformed samples.